The ability to modulate cell behavior through genetic modification has great potential as a therapeutic strategy, as well as providing a powerful tool for elucidating gene function (so-called functional genomics). Antisense oligonucleotides, which are most commonly single-stranded DNA molecules 15-25 nucleotides in length, modulate gene expression by binding to a complementary segment on the mRNA from the target gene. While antisense technology is becoming a viable therapeutic entity and platform for functional genomics, a major barrier to its widespread practice still exists: the delivery of the genetic material (polynucleic acid) to cells in a quantity that is biologically effective and in a form that is functionally intact, yet non-toxic. Our overall goal is to deliver antisense molecules selectively to a target cell type (hepatocytes), resulting in low-dose inhibition of expression of genes of interest. To achieve this goal, we will develop a new family of multifunctional DNA delivery vectors (multiplexes) using a combinatorial synthesis approach. These vectors will possess biomimetic polymers that condense DNA, cationic peptides that destabilize cellular membranes, and galactose moieties that target them to hepatocytes (primary liver cells). Vectors will be characterized for size, stability, and cytotoxicity. We will study the adsorption of these materials to target vs. non-target cells, and interpret the results in the framework of a colloid-chemical mathematical model, which will be used to refine and optimize the composition of the vectors. The effectiveness of these vectors to deliver gene expression-modulating antisense oligonucleotides will be evaluated and assessed to further refine the approach. W expect the long-term outcome to be a selective and efficient method for oligonucleotide delivery for therapeutic and functional genomics applications.